The interactions between endogenous peptides and specific target cells in the lung will be studied in vitro to determine how these interactions may relate to tissue injury and inflammation. Biologically active peptides from complement (anaphylatoxins) cause histamine release from mast cells and increase vascular permeability. One of the objectives of the proposed research is to determine their actions on endothelium. Another is to compare the responses of endothelial cells and mast cells to various endogenous vasoactive peptides, including anaphylatoxins kinins and peptides isolated from tissues. The overall, general objective is to determine mechanisms through which mast cells and endothelial cells participate in inflammatory reactions. Perfused lungs of small animals, will be used for determination of some actions of peptides on endothelium. Suspensions of rat mast cells and samples of chopped lung tissue will be used to determine the action on mast cells. Cultured endothelial cells collected from lungs of experimental animals and vessels of umbilical cords will also be used to answer these questions. 1. Do anaphylatoxins affect endothelium directly, or indirectly by causing release of histamine from mast cells? 2. Do anaphylatoxins or other peptides release substances from endothelium or do they stimulate pinocytosis and uptake of materials? 3. Do endothelial cells from lung bind or metabolize vasoactive peptides, particularly anaphylatoxins? 4. Do mast cells take up or inactivate peptides? 5. Does injured endothelium, or substances released from mast cells contribute to inflammation by activating complement or kinin systems in blood? 6. Can the actions of anaphylatoxins and other peptides on mast cells or endothelial cells be related to specific biochemical events and changes in cell function?